Ginseng Alternaria leaf and stem blight, caused by Alternaria panax, imposes substantial yield and economic losses to the ginseng cultivation industry. Current diagnostic methods for ginseng diseases primarily rely on pathogen isolation from infected tissues, a procedure that is laborious, time-consuming, and inherently low in sensitivity. This study has therefore developed a rapid, specific and sensitive SYBR Green-based quantitative real-time PCR (qPCR) assay for detecting A. panax in plants, seeds, and soil. The developed qPCR assay exhibited high sensitivity and repeatability, with a detection limit of 0.074 fg/μL of target amplicon DNA (0.619 ng/μL of genomic DNA) and a coefficient of variation below 2%. In artificially inoculated tissues (leaves, stems and seeds), Ct values decreased progressively with increasing incubation time, reflecting pathogen proliferation. Analysis of field-collected leaves and stems showed a strong overall correlation between Ct values and visual disease grades. Surveying of ginseng-growing areas revealed that A. panax was detected in asymptomatic leaves and stems at rates of 12.12% and 14.29%, respectively, and in 14.46% of soil samples and 23.73% of seed samples. This qPCR assay presented here provides a robust tool for forecasting early disease, tracking the primary inoculum of the pathogen and its transmission chains, and screening of both ginseng seed lots and candidate soils for ginseng Alternaria leaf and stem blight prior to planting.

INTRODUCTION:The fungal cell wall, a dynamic structure critical for pathogenesis, is composed of polysaccharides and proteins. UDP-glucose 4-epimerases (UGEs) play a pivotal role in cell wall synthesis by converting UDP-galactose between UDP-glucose. This study investigates the role of MoUGE1 in Magnaporthe oryzae pathogenesis and explores its potential as an antifungal target for fungal disease control. A lead inhibitor targeting MoUGE1 was identified through virtual screening. OBJECTIVES:The aims of this study were to elucidate the role of MoUGE1 in M. oryzae during rice blast pathogenesis, assess its potential as an antifungal target, and identify potential MoUGE1 inhibitors through virtual screening to control rice blast. METHODS:To analyses the role of MoUGE1 in M. oryzae, we generated Δuge1 mutants via split-PCR-mediated gene knockout. The impact of MoUGE1 on fungal growth, cell wall composition, and plant infection was assessed. Metabolomic analysis revealed the impact of MoUGE1 deletion on metabolic processes of rice blast. Structure-based virtual screening, molecular dynamics (MD) simulation and surface plasmon resonance (SPR) used to find hit compounds inhibiting MoUGE1. RESULTS:The Δuge1 exhibited reduced mycelial growth, altered cell wall and cell membrane composition, and impaired plant infection. Metabolomic analysis and western blot revealed accumulation in UDP-galactose and alteration of N-glycosylation, leading to cell wall instability and increased sensitivity to cell wall stressors. Virtual screening identified lig122132 as a potential MoUGE1 inhibitor, which was further confirmed through MD simulation and SPR, showing stable binding to the MoUGE1. CONCLUSION:Our findings emphasize the significance of MoUGE1 in fungal cell wall integrity, appressorium function, and virulence in M. oryzae. Identifying MoUGE1 as a target for antifungal intervention provides new insights into the molecular mechanisms of rice blast pathogenesis and paves the way for developing innovative strategies against this major agricultural disease. The potential MoUGE1 inhibitor, lig122132, is a promising starting point for the development of novel fungicides to control rice blast.

Rice blast disease, a major global threat to staple crops, is caused by the ascomycete fungus Magnaporthe oryzae. This pathogen has complex mechanisms to invade rice, with mitochondrial function crucial for infection energy. Our study looks at the impact of Mrm1, a putative rRNA methyltransferase, on mitochondrial dynamics and pathogenicity of M. oryzae. Mrm1 deficiency delays appressorium formation and reduces turgor pressure for host penetration and infection hypha expansion. The N-terminal sequence of Mrm1, with a mitochondrial targeting sequence (MTS), is vital for its localization and function. Deletions cause impaired growth and lower pathogenicity. Deleting MRM1 leads to abnormal mitochondrial morphology, with more filamentous mitochondria during invasive growth, disrupting the balance of fission and fusion. This imbalance reduces the fungus’s infection ability. Furthermore, loss of Mrm1 alters the steady-state protein levels of mitochondrial dynamics regulators Dnm1 and Fzo1, likely through translational regulation, while their transcript abundances remain unchanged. In the absence of Mrm1, the levels of these proteins are significantly reduced. Our findings deepen the understanding of epitranscriptomic regulation in fungal pathogenicity and represent a potential candidate for future target-based intervention strategies, pending validation through chemical or genetic approaches.

Plant disease control is trapped in a constant evolutionary competition between plants and pathogens. Pathogens evolve faster than we can breed resistance genes or register new fungicides (Singh et al., 2023). Notably, plants employ multiple immune strategies, including both disease resistance and tolerance, to protect their health (Tang et al., 2025), enriching the contextual understanding of plant defense mechanisms. Transgenic crops, while powerful, remain facing regulatory and public acceptance challenges in many regions, with regulatory timelines varying across global frameworks-extending 8-12 years in some Western countries, while China has established a structured evaluation system that balances safety and efficiency (Liang et al., 2022, 2025). Meanwhile, chemical control faces an accelerating loss of efficacy due to resistance and is increasingly incompatible with climate-smart and biodiversity-friendly farming mandates. We argue that it is time to decouple crop immunity from plant genetics altogether and outsource it to an editable, transient, and regulation-resilient microbial layer: the endophyte microbiome.

Epigenetic regulation, particularly RNA methylation, remains largely unexplored in plant-pathogenic fungi. This study investigates the role of 5-methylcytosine (m5C) RNA methylation during infection by Magnaporthe oryzae, the rice blast fungus, with an emphasis on its effects on autophagy. We identified Ncl1, an m5C RNA methyltransferase, as essential for fungal virulence and appressorium development. Using m5C RNA immunoprecipitation sequencing, we mapped the m5C landscape of the M. oryzae transcriptome, identifying 9014 hypomethylated peaks across 5678 genes in the Δncl1 mutant. RNA sequencing analysis revealed that 119 m5C-modified genes were upregulated and 199 were downregulated, indicating a key role for Ncl1 in regulating gene expression. Mechanistically, Ncl1-mediated m5C methylation stabilizes ATG5 and ATG16 mRNAs, which are essential for Atg8 lipidation, autophagosome formation, and full M. oryzae pathogenicity. Notably, Ncl1 protein stability is modulated by the Pmk1 signaling pathway through phosphorylation and Smt3-mediated SUMOylation. These findings reveal a complex interplay between epigenetic regulation and post-translational modifications in fungi. They highlight the central role of m5C RNA methylation in autophagy and pathogenicity in M. oryzae, enhance our understanding of fungal biology, and provide potential targets for antifungal strategies.

Colletotrichum asianum, the cause of mango anthracnose, is a major threat to mango production worldwide. However, the mechanisms underlying plant invasion by C. asianum are poorly understood. Mini-chromosomes are increasingly recognised as indispensable components in the virulence of plant-pathogenic fungi. Here, we identify CaMutA, a secreted glycoside hydrolase 71 effector encoded on a mini-chromosome, as a critical pathogenicity factor that suppresses plant immune responses and is essential for infection by C. asianum. CaMutA directly interacts with the mango chitinase MiChi1. When heterologously expressed in Arabidopsis thaliana, MiChi1 confers enhanced resistance against multiple pathogens, suggesting its role in plant defence, a process that CaMutA subverts. Together, our findings uncover that a mini-chromosome-encoded effector can subvert plant immunity by directing the ubiquitin-mediated degradation of conserved defence-related chitinases. This study thus identifies promising targets for controlling mango anthracnose.

Plant pathogenic fungi pose a severe threat to global agriculture, causing substantial yield losses in staple crops and jeopardizing food safety through mycotoxin contamination. Conventional fungicide development is hindered by high costs, lengthy timelines, and the rapid evolution of fungal resistance, which outpaces conventional discovery workflows. Although artificial intelligence (AI) offers transformative potential to address these bottlenecks, its application in plant pathology remains fragmented and lacks integration of agriculture-specific constraints such as field stability, ecological safety, and resistance management. This review introduces the AI-driven fungicide design (AIFD) platform, a comprehensive framework comprising four interdependent components: a plant pathogen-specific data ecosystem, a modular microservice technical architecture, a linear multiphase development workflow, and a specialized resistance prediction workflow. We synthesize key technological advances across the fungicide development pipeline, from target identification and virtual screening to molecular optimization and field validation, with an emphasis on AI methodologies adapted to agrochemical requirements rather than pharmaceutical standards. Despite substantial advances, critical challenges persist, including scarce high-quality training data for understudied pathogens, limited model adaptability across diverse agroecosystems, poor interpretability that hinders stakeholder trust, and accessibility barriers for resource-constrained researchers. Future directions emphasize the integration of real-time field data, explainable AI to facilitate regulatory acceptance, and inclusive design strategies aimed at bridging the laboratory-to-field gap. By aligning computational innovation with agricultural priorities, AIFD platforms can accelerate the discovery of resistance-breaking, environmentally benign fungicides, thus offering a viable pathway toward sustainable crop protection and enhanced global food security.

Mitochondria generate ATP through oxidative phosphorylation (OXPHOS), with core structural subunits encoded by mitochondrial DNA (mtDNA) and translated by mitochondrial ribosomes. However, how mitochondrial translation elongation influences OXPHOS biogenesis remains unclear. Here, we show that in Neurospora crassa, the mitochondrial ribosomal RNA (rRNA) methyltransferase 1 (MRM1) promotes OXPHOS biogenesis by repressing translation elongation independently of its catalytic activity. The N-terminal intrinsically disordered region (IDR) of MRM1 binds simultaneously to mitochondrial ribosomes and mRNAs. Disrupting either interaction accelerates elongation and enhances synthesis of mtDNA-encoded OXPHOS subunits but impairs their co-translational folding and membrane insertion. Pharmacological slowing of mitochondrial translation partially alleviates these defects. The MRM1 IDR is conserved in Ascomycete fungi and is essential for plant infection by Magnaporthe oryzae. Together, our findings identify translation elongation control as a mechanism coordinating mitochondrial protein synthesis and folding during OXPHOS biogenesis and MRM1 as a potential target for broad-spectrum antifungal strategies.

Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4), the causal agent of Fusarium wilt, poses a serious threat to global banana and plantain production. This study investigated the toxicological impact of 1,4-dichlorobenzene (p-DCB), a halogenated aromatic compound from biocontrol bacteria Streptomyces misionensis TF78, on the virulent Foc TR4 strain, combining morphological and transcriptomic analyses. Fungal mycelia were exposed to 2.67 g/L p-DCB for 12, 48, and 96 h, separately, after which structural alterations and gene expression changes were evaluated. Genome-wide transcriptional profiles were characterized using RNA sequencing, and 20 differentially expressed genes (DEGs) were validated through quantitative real-time PCR (qRT-PCR). The results demonstrated that p-DCB treatment significantly (p < 0.01) reduced the colony growth diameter of Foc TR4 and caused severe mycelial damage, structural ablation, a significant decrease in spore germination rates (p < 0.01), and a 38–62

BACKGROUND:The development of biocontrol agents represents a promising strategy to manage banana Fusarium wilt, caused by Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4). Although many traditional approaches have isolated beneficial microorganisms from soil or the rhizosphere, studies seeking biocontrol resources from the perspective of banana root endophytes remain scarce. RESULTS:Endophytic microbiome analysis revealed significant enrichment of Bacillota in the wilt-resistant cultivar. Among the isolated strains, Bacillus velezensis JDB15 exhibited the best inhibitory effect against Foc TR4. The fermentation broth of JDB15 significantly inhibited spore germination and caused hyphal membrane damage in pathogens. Mechanistic studies indicated that the lipopeptide surfactin C is a candidate active antimicrobial metabolite produced by JDB15, which disrupts pathogen cell membrane integrity, increases membrane permeability, and induces electrolyte leakage. Another isolated endophytic fungus, Trichoderma harzianum strain JDL4, also exhibited strong antagonistic activity against Foc TR4 probably through mycoparasitism. Combined application of cell-free filtrate from JDB15 and JDL4 demonstrated effective control against multiple plant diseases including banana Fusarium wilt, tomato Fusarium wilt, corn southern leaf blight, and rice blast under controlled conditions. CONCLUSION:We suggest that the antimicrobial activity of JDB15 and JDL4 is most probably attributable to the metabolite surfactin C and likely mycoparasitism, respectively. Co-application of the fermentation filtrates of these two strains exhibited broad-spectrum disease control efficacy and significantly improved disease suppression compared with either strain alone. These findings provide novel biological agents for the control of banana Fusarium wilt and other plant diseases. © 2026 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Poly(A) tail shortening by deadenylases is a central checkpoint linking mRNA fate to eukaryotic development, yet its impact on fungal pathogenesis remains unexplored. Here, we uncover that the Pan2-Pan3 deadenylase complex is a master regulator of infection in the rice blast fungus Magnaporthe oryzae. Pan2 and Pan3 form a catalytically active complex that localizes to P-bodies and globally trims poly(A) tails to enforce mRNA quality control. Deletion of either or both subunits abolishes this quality-control checkpoint, causing severe virulence loss due to arrested appressorium maturation, disrupted glycogen/lipid mobilization, and impaired autophagy. Integrating poly(A)-seq and transcriptome profiling reveals 390 mRNAs whose poly(A) tails are ≥ 5 nt longer and whose steady-state levels are elevated in the Δpan2Δpan3 mutant; among them, ATG5, GLS2, and DES1-key genes governing autophagy, ER quality control, and ROS detoxification respectively-are directly deadenylated by Pan2-Pan3. Loss of deadenylation destabilizes these mRNAs and reduces their protein output, thereby crippling infection. Our findings establish Pan2-Pan3 complex-mediated deadenylation as an essential post-transcriptional layer that orchestrates fungal virulence through stringent mRNA quality control, offering a novel target for crop protection.

Pathogen-induced reactive oxygen species act as key signaling molecules in plant immunity, but their integration with epigenetic regulation remains unclear. Here, we identify the rice (Oryza sativa) histone deacetylase OsHDA705 as a redox sensor that coordinates immunity through oxidative post-translational modifications. Pathogen-induced reactive oxygen species oxidizes OsHDA705 at cysteine 256, blocking its deacylase activity. This oxidation promotes hyperacylation of the transcription factor OsIPA1 and histones, thereby activating defense gene expression. We further show that the catalase OsCATB functions as a redox mediator, reducing oxidized OsHDA705 to restore its deacetylase activity, thereby reestablishing the suppression of immunity. The fungal pathogen Ustilaginoidea virens hijacks this process via the secreted effector UvSE1, which physically interacts with the host catalase OsCATB to boost its reactive oxygen species-scavenging activity, thereby reducing the oxidation level of OsHDA705. Genetic disruption of the OsCATB-OsHDA705 module enhances broad-spectrum disease resistance. Our findings reveal a pathogen strategy to reprogram the host's redox-epigenetic regulation and establish reversible histone deacetylase oxidation as a molecular switch regulating immune transcription in plants.

Hydrogen sulfide (H2S) regulates cellular activities in plants and mammals through S-sulfhydration, a post-translational modification of proteins. The role of H2S and its molecular targets in fungi, however, remains unclear. Here we show that H2S, synthesized by cystathionine γ-lyase (CSE1) in the rice blast fungus Magnaporthe oryzae, is essential for optimal fungal infection. Excessive H2S, through S-sulfhydration, impairs fungal infectivity by inhibiting autophagy. Using quantitative proteomics, we identify numerous S-sulfhydrated proteins in M. oryzae, including the autophagy-related protein ATG18. S-sulfhydration of a cysteine residue (Cys78) in ATG18 is essential for its binding to phosphatidylinositol 3-phosphate, thereby maintaining the protein's structural stability and regulating autophagy. Thus, our study reveals a mechanism by which H2S-mediated S-sulfhydration controls autophagy in the rice blast fungus and suggests the potential use of H2S donors as a strategy to control fungal diseases by targeting fungal development and infection structures.

Thiolation, a post-transcriptional modification catalyzed by Uba4-Urm1-Ncs2/Ncs6 pathway in three specific transfer RNAs (tRNAs), is conserved from yeast to humans and plays an important role in enhancing codon-anticodon interaction and translation efficiency. Yet, except for affecting effector secretion, its roles in plant pathogenic fungi are not fully understood. Here, we used Magnaporthe oryzae as a model system to illustrate the vital role of s2U34 modification on the appressorium-mediated virulence. The absence of tRNA thiolation leads to diminished translation elongation at AAA/CAA/GAA but not their synonymous codons, resulting in reduced levels of key proteins enriched in these codons, which are critical for appressorium development and function. Importantly, overexpressing these proteins can partially mitigate the defects resulting from NCS2 deletion. Our study sheds light on the s2U34 modification's role in plant pathogenic fungi, enhancing our understanding of translational control beyond effector secretion.

Sucrose is a key quality trait in peanuts, yet high-sucrose varieties are scarce. Although sucrose transporters (SUT/SUC) play crucial roles in sucrose transport and accumulation during seed development, systematic analyses in peanuts are limited. This study conducted a genome-wide analysis of the SUC gene family in cultivated peanut (Arachis hypogaea L.). Sixteen AhSUC genes were identified and characterized for genomic distribution, phylogeny, and expression across tissues and developmental stages. The genes are unevenly distributed across the genome with clustered chromosomal localization. All AhSUC proteins contain the conserved sucrose/proton co-transporter domain (IPR005989), exhibit the typical 12 transmembrane α-helical structure of the major facilitator superfamily, are hydrophobic, and predicted to localize to the membrane. Promoter analysis revealed cis-regulatory elements associated with growth, development, light, hormone, and stress responses. Expression profiling showed tissue-specific patterns, with eight AhSUC genes being highly expressed in cotyledons and embryos. Comparative analysis between high-sugar and conventional varieties showed higher expression of AhSUC2, AhSUC9, and AhSUC11 in the high-sugar variety, correlating with increased sucrose accumulation. Functional validation using a sucrose transport-deficient yeast mutant confirmed the sucrose transport activity of these genes. These findings provide insight into sucrose accumulation mechanisms and offer genetic targets for breeding high-sugar peanut varieties.

Transfer RNA (tRNA) modifications refer to the chemical alterations that occur on tRNA molecules, which are essential for their structure, stability, and function. These modifications have been shown to play crucial roles in diverse biological processes across different organisms. Recent studies have highlighted that specific tRNA modifications are directly linked to virulence traits and infection processes in plant pathogenic fungi. This review aims to explore their roles in fungal biology and pathogenicity, summarize the current understanding of the molecular mechanisms of tRNA modification in plant pathogenic fungi, and discuss the potential implications for developing novel antifungal strategies.

Mango (Mangifera indica L.), tropical fruit renowned for its rich flavor and nutritional benefits, is extensively cultivated in southern China (Wang et al. 2023). In July 2023, leaf spots were observed in a mango plantation located in Tianyang, Guangxi, China (106°22'-107°09'E, 23°29'-24°07'N), with ~20% incidence across surveyed fields. Affected leaves exhibited 20-80% necrotic coverage, with subcircular or irregular yellowish-brown lesions gradually expanding into brown irregular areas surrounded by yellow halos. Symptomatic leaves were collected from three orchards, and 5 × 5 mm sections were excised from lesion margins and surface sterilized by immersion in 75% ethanol for 15 s and 2% sodium hypochlorite for 1 min, followed by three sterile distilled water rinses. Disinfected tissues were placed on potato dextrose agar (PDA) and incubated at 28°C under 12-h photoperiod cycles for 5 days. A total of 75 morphologically similar isolates were obtained, and three representative strains (TY6-1, TY8-1, TY9-1) were selected for characterization. Colonies displayed dark green pigmentation with granular textures and irregular white margins. Conidiomata were black, immersed or semi-immersed, subglobose to ellipsoidal, solitary or aggregated on the stroma, with circular ostioles. Conidiogenous cells appeared stick-shaped with apical constrictions, producing hyaline, unicellular, ovoid or subglobose conidia (6.0-8.5 × 8.5-13.3 μm; n=90) bearing single apical appendages. Morphological characteristics of the three isolates aligned with descriptions of Phyllosticta spp. (Wikee et al. 2013). For molecular identification, the internal transcribed spacer (ITS) region, actin (ACT), and translation elongation factor (TEF) genes were amplified and sequenced using primer pairs ITS-ITS1/ITS4, ACT-512F/783R, and TEF-728F/986R, respectively (White et al. 1990; Carbone et al. 1999). Sequences were deposited in GenBank under accession numbers PV259393-PV259395 (ITS); PV268325-PV268327 (ACT); and PV268328-PV268330 (TEF). BLASTN analyses revealed that all sequences exhibited over 99% identity with sequences (accessions JF261465, JF343647, JF261507) of the type strain of P. capitalensis (CBS 128856). Maximum likelihood phylogeny (RAxML v8.2.10) of concatenated sequences placed all isolates within the P. capitalensis clade with strong bootstrap support. Pathogenicity assays were conducted on leaves of two-year-old mango plants in a greenhouse. Both wounded and intact leaves (20 leaves/plant, 3 plants/treatment) were inoculated with 20 μL of conidial suspension (10⁶ spores/mL), while controls received 0.05% Tween 80. Plants were covered with plastic bags to maintain high humidity. After 14 days, wounded and inoculated leaves developed lesions matching field observations, whereas control and unwounded leaves remained asymptomatic. The pathogenicity test was repeated three times with similar results. Koch's postulates were fulfilled by re-isolation of P. capitalensis from symptomatic tissues, confirmed through morphological and molecular congruence. Although P. capitalensis has been reported to cause leaf spot on Hymenocallis littoralis (Wu et al. 2024) and Rubus chingii (Zhang et al. 2022), to our knowledge this is the first report of mango leaf spot caused by P. capitalensis in China. This finding provides critical insights for developing targeted management strategies against emerging mango leaf spot epidemics.

Macroautophagy/autophagy is essential to the pathogenicity of Magnaporthe oryzae. Phosphatidylinositol-4-phosphate (PtdIns4P) is a key lipid involved in the autophagy process. Recent studies have shown that the PtdIns4P pool on autophagic membranes is crucial to autophagosome biogenesis and fusion with the vacuole; however, the mechanism regulating the PtdIns4P levels on autophagic membranes is still unclear. Here, we report that two oxysterol-binding protein-related proteins, MoOrp1 and MoOrp2, required for the pathogenicity in M. oryzae, function as PtdIns4P transporters to modulate the autophagy process. We found that simultaneous knockout of MoORP1 and MoORP2 genes (△Moorp1-2) led to a range of defects in autophagy-related infection processes, including lipid degradation and autophagic cell death in conidia, generation of appressorial turgor pressure required for host penetration, and growth of infectious hyphae in plant cells. Autophagy flux assays of the △Moorp1-2 strain revealed a prominent deficiency in autophagosome formation and fusion with the vacuole. Molecular analyses showed that both MoOrp1 and MoOrp2 could bind PtdIns4P and be recruited to the autophagosome by interacting with MoAtg8. Disruption of the two MoORP genes impeded the autophagy-induced PtdIns4P accumulation on the autophagosome and vacuolar membrane. Disturbance of the molecular features vital for PtdIns4P-binding activity in MoOrp1 and MoOrp2 abolished their function in autophagy and pathogenicity. Hence, our study uncovers new roles of the Atg8 protein and highlights the significance of the MoOrp-mediated PtdIns4P translocation in regulating autophagy and pathogenicity in M. oryzae.Abberivations: Atg: autophagy related; BiFC: bimolecular fluorescence complementation; CHOL: cholesterol; CM: complete medium; CL: cardiolipin; Co-IP: co-immunoprecipitation; DAG: diacylglycerol; FDA: fluorescein diacetate; GABARAP: GABA type A receptor-associated protein; GFP: green fluorescent protein; hpi: hours post inoculation; IH: invasive hypha; LDs: lipid droplets; MM-N: minimum medium minus nitrogen; Mo: Magnaporthe oryzae; ORPs: oxysterol-binding protein-related proteins; OSBP: oxysterol-binding protein; ORD: OSBP-related domain; PAS: phagophore assembly site; PA: phosphatidic acid; PS: phosphatidylserine; PE: phosphatidylethanolamine; PC: phosphatidylcholine; PG: phosphatidylglycerol; PtdIns: phosphatidylinositol; PIs: phosphoinositides; PtdIns4Ks: phosphatidylinositol 4-kinases; PtdIns3P: phosphatidylinositol-3-phosphate; PtdIns4P: phosphatidylinositol-4-phosphate; PtdIns(3,5)P2: phosphatidylinositol-3,5-bisphosphate; PtdIns(4,5)P2: phosphatidylinositol-4,5-bisphosphate; PM: plasma membrane; SM: sphingomyelin; ST: sulfatide; TG: triglyceride; TOR: target of rapamycin; YFP: yellow fluorescent protein.

TANK-binding kinase 1 (TBK1) is a key signaling kinase involved in innate immune and inflammatory responses. TBK1 drives immune cells to participate in the inflammatory response by activating the NF-κB and interferon regulatory factor signaling pathways in immune cells, promoting the expression of pro-inflammatory genes, and regulating immune cell function. Thus, it plays a crucial role in initiating a signaling cascade that establishes an inflammatory environment. In inflammation-related diseases, TBK1 acts as a bridge linking inflammation to immunity, metabolism, or tumorigenesis, playing an important role in the pathogenesis of immune-mediated inflammatory diseases, metabolic, inflammatory syndromes, and inflammation-associated cancers by regulating the activation of inflammatory pathways and the production of inflammatory cytokines in cells. In this review, we focused on the mechanisms of TBK1 in immune cells and inflammatory-related diseases, providing new insights for further studies targeting TBK1 as a potential treatment for inflammation-related diseases. Thus, optimizing and investigating highly selective cell-specific TBK1 inhibitors is important for their application in these diseases.

Rice blast disease, caused by Magnaporthe oryzae, significantly threatens global rice yields. The Pmk1-MAPK signaling pathway is crucial for the infection process, but the precise regulatory mechanisms of Pmk1 remain unclear. Our research reveals that sumoylation of Pmk1 is vital for its infectious function. A sumoylation site at K347 and two small ubiquitin-related modifier (SUMO)-interacting motifs (SIMs) in Pmk1 are highly conserved across fungi. This sumoylation, orchestrated by Smt3 and Siz1, reduces the phosphorylation of Pmk1 by tuning its interaction with Mst7. The Pmk1 sumoylation is high in hyphae and less in conidia, and it intensifies during appressorium maturation. It may act as a molecular brake to prevent excessive Pmk1 phosphorylation during appressorium formation, without affecting phosphatase Pmp1 or the localization of Pmk1. Mutations at K347 lead to hyperphosphorylation of Pmk1 and Mst12, and overexpression of appressorium-related genes. The Δpmk1/Pmk1K347R mutant shows deficiencies in storage utilization, turgor accumulation, and septin ring formation. Our study highlights the critical role of sumoylation dynamically balancing Pmk1 function via phosphorylation crosstalk, crucial for infection of M. oryzae, thus proposing a conserved target for antifungal strategies across fungal pathogens.